7S6L

J08 fragment antigen binding in complex with SARS-CoV-2-6P-Mut7 S protein (conformation 3)

Summary for 7S6L

• Entry DOI: 10.2210/pdb7s6l/pdb
• EMDB information: 24879
• Descriptor: Spike glycoprotein, J08 fragment antigen binding heavy chain variable domain, J08 fragment antigen binding light chain variable domain, ... (5 entities in total)
• Functional Keywords: covid, sars, cov-2, viral glycoprotein, spike, stabilizing mutations, coronavirus, ultrapotent antibody, neutralizing antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 5
• Total formula weight: 455709.37

Authors

Ozorowski, G.,Torres, J.L.,Ward, A.B. (deposition date: 2021-09-14, release date: 2022-05-11, Last modification date: 2024-10-23)

Primary citation

Torres, J.L.,Ozorowski, G.,Andreano, E.,Liu, H.,Copps, J.,Piccini, G.,Donnici, L.,Conti, M.,Planchais, C.,Planas, D.,Manganaro, N.,Pantano, E.,Paciello, I.,Pileri, P.,Bruel, T.,Montomoli, E.,Mouquet, H.,Schwartz, O.,Sala, C.,De Francesco, R.,Wilson, I.A.,Rappuoli, R.,Ward, A.B.
Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody.
Proc.Natl.Acad.Sci.USA, 119:e2120976119-e2120976119, 2022

PubMed Abstract: As the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs). Here, we evaluate the potency of the previously described mAb J08 against these variants using cell-based assays and delve into the molecular details of the binding interaction using cryoelectron microscopy (cryo-EM) and X-ray crystallography. We show that mAb J08 has low nanomolar affinity against most VoCs and binds high on the receptor binding domain (RBD) ridge, away from many VoC mutations. These findings further validate the phase II/III human clinical trial underway using mAb J08 as a monoclonal therapy.

PubMed: 35549549
DOI: 10.1073/pnas.2120976119

Experimental method

ELECTRON MICROSCOPY (4 Å)